The major problem or barrier is that there are currently no methods or approaches to adequately address prostate cancer health disparity in African Americans. A major question is why do African American men have a higher overall incidence, earlier age of onset, increased proportion of clinically advanced disease and increased bone metastases and mortality from prostate cancer compared to Caucasians? The main goal of this project is to investigate the genetic basis of prostate cancer health disparities The rationale is that prostate cancer is the leading cancer among men of African descent in the USA. Despite more aggressive screening of prostate cancer across all demographics in the United States, disparities among populations persist. A substantial proportion of African American men have a higher overall incidence, earlier age of onset, increased proportion of clinically advanced disease and increased bone metastases and mortality from prostate cancer compared to Caucasians. There are racial disparities in survival after diagnosis of prostate cancer in men. Therefore, prostate cancer incidence and mortality represent a significant public health problem in African American men. Recent studies have shown that miRNAs are significantly altered in prostate cancer. Based on our preliminary data, we hypothesize that the differential expression profile of a set of oncogenic miRNAs and tumor suppressor miRNAs in African Americans may target a set of prostate cancer specific genes and may contribute to the prostate cancer health disparity in African Americans. The molecular mechanisms of action of tumor suppressor miRNAs are through repressing oncogenes and activating tumor suppressor genes. We will test these hypotheses through analyses of a series of experiments proposed under our specific aims. All the aims are highly focused, centralized, innovative, clinically significant, functional and mechanistic in nature. Specific Aim # 1. Investigate the role of miRNAs as the genetic basis of prostate cancer health disparity in African Americans as compared to Caucasians. Specific Aim # 2. Investigate the functional significance and molecular mechanisms of action of oncogenic and tumor suppressor miRNAs in race-related prostate cancer. Specific Aim # 3. Investigate the molecular mechanisms of differential expression of miRNAs in African Americans and Caucasians. Impact: The present application has high impact because it describes a novel concept and approach that is different and better from the previous attempts since differential expression of a set of miRNAs may explain why African Americans have higher incidence of prostate cancer compared to Caucasians. This project will identify novel miRNAs that can be used as genetic biomarkers and potential therapeutic targets for race-related prostate cancer.